Asset Details
Do you wish to reserve the book?
Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC
Do you wish to request the book?
Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC
2024
Overview
Acquired resistance remains a bottleneck for molecular‐targeted therapy in advanced hepatocellular carcinoma (HCC). Metabolic adaptation and epigenetic remodeling are recognized as hallmarks of cancer that may contribute to acquired resistance. In various lenvatinib‐resistant models, increased glycolysis leads to lactate accumulation and lysine lactylation of IGF2BP3. This lactylation is crucial for capturing PCK2 and NRF2 mRNAs, thereby enhancing their expression. This process reprograms serine metabolism and strengthens the antioxidant defense system. Additionally, altered serine metabolism increases the availability of methylated substrates, such as S‐adenosylmethionine (SAM), for N6‐methyladenosine (m6A) methylation of PCK2 and NRF2 mRNAs. The lactylated IGF2BP3‐PCK2‐SAM‐m6A loop maintains elevated PCK2 and NRF2 levels, enhancing the antioxidant system and promoting lenvatinib resistance in HCC. Treatment with liposomes carrying siRNAs targeting IGF2BP3 or the glycolysis inhibitor 2‐DG restored lenvatinib sensitivity in vivo. These findings highlight the connection between metabolic reprogramming and epigenetic regulation and suggest that targeting metabolic pathways may offer new strategies to overcome lenvatinib resistance in HCC. This study reveals that in lenvatinib‐resistant hepatocellular carcinoma, increased glycolysis results in lactate accumulation and lysine lactylation of IGF2BP3, which increase the expression of PCK2 and NRF2. This leads to a reprogramming of serine metabolism, S‐adenosylmethionine (SAM) production, RNA m6A modification, and the antioxidant system. The IGF2BP3 lactylation‐PCK2‐SAM‐m6A loop sustains the upregulation of PCK2 and NRF2 expression and ultimately confers lenvatinib resistance.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Antineoplastic Agents - pharmacology
/ Antineoplastic Agents - therapeutic use
/ Carbon
/ Carcinoma, Hepatocellular - drug therapy
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - metabolism
/ Cells
/ Drug Resistance, Neoplasm - drug effects
/ Drug Resistance, Neoplasm - genetics
/ Glucose
/ Humans
/ Kinases
/ Liver Neoplasms - drug therapy
/ Liver Neoplasms - metabolism
/ Mice
/ PCK2
/ Phenylurea Compounds - pharmacology
/ Phenylurea Compounds - therapeutic use
/ Proteins
/ RNA-Binding Proteins - genetics
